Ark breakthrough may increase cancer therapies efficacy
progression with significantly smaller chemotherapy doses opening
the way to reduce the side effects as well as increase the efficacy
of anti cancer therapies.
"These results indicate the potential to improve the therapeutic effect and to reduce the unpleasant side-effects of a wide variety of drugs, most obviously chemotherapy and other potent anti-cancer agents, but also in many other therapies where the side-effects are high and thus dose-limiting," said Nigel Parker, CEO of Ark.
Ark's latest research results are from two cancer treatment models where aggressive tumours developed rapidly under the skin. Scavidin DNA in a viral delivery vector was transfected into the growing tumours.
Two different treatments were then given intravenously at sub-therapeutic doses, biotin-tagged Yttrium90 (a radio isotope) and biotin-tagged paclitaxel (a potent generic chemotherapy).
Each treatment eliminated tumour growth during the respective 7-10 day study periods with a clear treatment response quickly evident.
Tumours in non-treated controls showed a three to five fold increase in size in the same period. No side-effects were observed.
The Company now plans to optimise the dosing regimes and explore efficacy in other cancer models, as well as exploring the full concentration gradient capabilities of Scavidin.
It will also commence final pre-clinical toxicity work prior to entering human studies after consulting with the regulators.
"Scavidin targeting technology offers the possibility of cancer patients being given up to a 10 times lower dose of radiation or chemotherapy than in conventional treatment approaches, which could markedly reduce the side-effects and enable the treatment to be repeated more easily," said Professor Seppo Ylä-Herrtuala, Ark's director of Molecular Medicine.
"An additional advantage is that the anti-cancer drug can be concentrated into the tumour at higher levels and thus its biological cancer 'killing' efficacy can be very substantially increased."
Ark's Scavidin is a novel two-part drug targeting technology originating from the DNA, which expresses the scavenger receptor on white blood cells.
This natural receptor usually collects undesired fats and damaged cells and membranes from the blood, taking them into the white blood cells and releasing them for destruction as part of the body's natural 'clean up' system.
By modifying the DNA sequence for such receptor types, Ark has developed a new family of receptors, which specifically bind only to the protein biotin, a naturally occurring substance that can easily be attached to therapeutic agents.
The Scavidin DNA is put into the tumour where it expresses the new drug targeting receptor. The therapeutic agent, pre-tagged with biotin, is then given intravenously at low doses.
As the therapeutic agent circulates round the body, Scavidin extracts it from the blood by binding to the biotin tag, taking it into the cell and releasing it. The receptor then goes back and collects more.
This 'molecular shuttle' system concentrates the therapeutic agent from a low and ineffective dose in the blood to a high therapeutic dose specifically in the target tissue.
In this way an effective therapeutic, which could have a poor safety profile (such as chemotherapy with high unwanted side-effects) at a traditional dose, may be given in a low and safe dose systemically, concentrating it specifically at the disease site where its treatment effect is needed.
Scavidin is able to concentrate a range of different biotinylated agents from small radioisotopes like Technetium99m and Yttrium90, through larger molecules like ferritin complexes and horseradish peroxidase stain and paclitaxel to large organic molecules like immunoglobulin.
